tbuckley/cabot-search huggingface dataset:
Cutaneous Involvement in Catastrophic Antiphospholipid Syndrome in a Multicenter Cohort of 65 Patients
Authors: Anastasia Dupré, Nathalie Morel, Cécile Yelnik, Philippe Moguelet, Véronique Le Guern, Romain Stammler, Yann Nguyen, Romain Paule, Virginie Dufrost, Felix Ackermann, Ygal Benhamou, Bertrand Godeau, Marc Lambert, Pierre Duffau, Arsène Mekinian, David Saadoun, Luc Mouthon, Eric Hachulla, Hélène Maillard, Hervé Levesque, Sandrine Morell-Dubois, Gaëlle Leroux, Jean-Charles Piette, François Chasset, Nathalie Costedoat-Chalumeau
Journal: JAMA Dermatology (2022)

Catastrophic antiphospholipid syndrome (CAPS) is a severe, rare complication of antiphospholipid syndrome (APS), but cutaneous involvement has not yet been adequately described.To describe cutaneous involvement during CAPS, its clinical and pathological features, and outcomes.This cohort study was a retrospective analysis of patients included in the French multicenter APS/systemic lupus erythematosus register (ClinicalTrials.gov: NCT02782039) by December 2020. All patients meeting the revised international classification criteria for CAPS were included, and patients with cutaneous manifestations were analyzed more specifically.Clinical and pathological data as well as course and outcome in patients with cutaneous involvement during CAPS were collected and compared with those in the register without cutaneous involvement.Among 120 patients with at least 1 CAPS episode, the 65 (54%) with skin involvement (43 [66%] women; median [range] age, 31 [12-69] years) were analyzed. Catastrophic antiphospholipid syndrome was the first APS manifestation for 21 of 60 (35%) patients with available data. The main lesions were recent-onset or newly worsened livedo racemosa (n = 29, 45%), necrotic and/or ulcerated lesions (n = 27, 42%), subungual splinter hemorrhages (n = 19, 29%), apparent distal inflammatory edema (reddened and warm hands, feet, or face) (n = 15, 23%), and/or vascular purpura (n = 9, 14%). Sixteen biopsies performed during CAPS episodes were reviewed and showed microthrombi of dermal capillaries in 15 patients (94%). These lesions healed without sequelae in slightly more than 90% (58 of 64) of patients. Patients with cutaneous involvement showed a trend toward more frequent histologically proven CAPS (37% vs 24%, P = .16) than those without such involvement, while mortality did not differ significantly between the groups (respectively, 5% vs 9%, P = .47).In this cohort study, half the patients with CAPS showed cutaneous involvement, with a wide spectrum of clinical presentations, including distal inflammatory edema. Skin biopsies confirmed the diagnosis in all but 1 biopsied patient.
Chronic spontaneous urticaria: Focus on pathophysiology to unlock treatment advances
Authors: Allen Kaplan, Mark Lebwohl, Ana M. Giménez‐Arnau, Michihiro Hide, April W. Armstrong, Marcus Maurer
Journal: Allergy (2022)

Abstract Chronic spontaneous urticaria (CSU) is a debilitating skin disease characterized by intensely itchy wheals, angioedema, or both. Symptoms recur spontaneously, on a near‐daily basis, over &gt;6 weeks; many patients experience flare‐ups over several years and, consequently, reduced quality of life. Differences between the inflammatory profiles of the skin of CSU patients (wheals and nonlesional sites) and healthy controls indicate that key drivers such as mast cells, eosinophils, and basophils interact, release vasoactive mediators, and prime the skin, leaving patients predisposed to symptoms. Many cytokines and chemokines involved in these inflammatory networks and their corresponding intracellular signaling cascades have been identified. These insights informed the development of therapies such as omalizumab, dupilumab, and Bruton's tyrosine kinase (BTK) inhibitors, marking a renewed focus on pathogenesis in CSU clinical research. Despite progress, current therapies provide symptomatic control but do not appear to redress the inflammatory balance in the skin permanently. A deeper understanding of CSU pathogenesis will permit a more targeted approach to developing novel treatments with curative intent. Here, we review what is known about the pathogenesis of CSU and consider how this can be used to identify rational targets to improve patient care further.
Novel FOXF1-Stabilizing Compound TanFe Stimulates Lung Angiogenesis in Alveolar Capillary Dysplasia
Authors: Arun Pradhan, Lixiao Che, Vladimir Ustiyan, Abid A. Reza, Nicole M. Pek, Yufang Zhang, Andrea B. Alber, Timothy R. Kalin, Jennifer A. Wambach, Mingxia Gu, Darrell N. Kotton, Matthew E. Siefert, Assem G. Ziady, Tanya V. Kalin, Vladimir V. Kalinichenko
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is linked to heterozygous mutations in the
Evaluation of Pressing Issues in Ecological Momentary Assessment
Authors: Arthur A. Stone, Stefan Schneider, Joshua M. Smyth
Journal: Annual Review of Clinical Psychology (2022)

The use of repeated, momentary, real-world assessment methods known as the Experience Sampling Method and Ecological Momentary Assessment (EMA) has been broadly embraced over the last few decades. These methods have extended our assessment reach beyond lengthy retrospective self-reports as they can capture everyday experiences in their immediate context, including affect, behavior, symptoms, and cognitions. In this review we evaluate nine conceptual, methodological, and psychometric issues about EMA with the goal of stimulating conversation and guiding future research on these matters: the extent to which participants are actually reporting momentary experiences, respondents’ interpretation of momentary questions, the use of comparison standards in responding, efforts to increase the EMA reporting period beyond the moment to longer periods within a day, training of EMA study participants, concerns about selection bias of respondents, the impact of missing EMA assessments, the reliability of momentary data, and for which purposes EMA might be considered a gold standard for assessment. Resolution of these issues should have far-reaching implications for advancing the field.
Effect of CGM Access Expansion on Uptake Among Patients on Medicaid With Diabetes
Authors: Kevin Ni, Carolyn A. Tampe, Kayce Sol, Douglas B. Richardson, Rocio I. Pereira
Journal: Diabetes Care (2022)

OBJECTIVE Current studies on continuous glucose monitor (CGM) uptake are revealing for significant barriers and inequities for CGM use among patients from socially underprivileged communities. This study explores the effect of full subsidies regardless of diabetes type on CGM uptake and HbA1c outcomes in a U.S. adult patient population on Medicaid. RESEARCH DESIGN AND METHODS This retrospective cohort study examined 3,036 adults with diabetes enrolled in a U.S. Medicaid program that fully subsidized CGM. CGM uptake and adherence were assessed by CGM prescription and dispense data, including more than one fill and adherence by medication possession ratio (MPR). Multivariate logistic regression evaluated predictors of CGM uptake. Pre- and post-CGM use HbA1c were compared. RESULTS CGM were very well received by both individuals with type 1 diabetes and individuals with type 2 diabetes with similar high fill adherence levels (mean MPR 0.78 vs. 0.72; P = 0.06). No significant difference in CGM uptake outcomes were noted among major racial/ethnic groups. CGM use was associated with improved HbA1c among those with type 2 diabetes (−1.2% [13.1 mmol/mol]; P &amp;lt; 0.001) that was comparable between major racial/ethnic groups and those with higher fill adherence achieved greater HbA1c reduction (−1.4% [15.3 mmol/mol]; P &amp;lt; 0.001) compared with those with lower adherence (−1.0% [10.9 mmol/mol]; P &amp;lt; 0.001). CONCLUSIONS CGM uptake disparities can largely be overcome by eliminating CGM cost barriers. CGM use was associated with improved HbA1c across all major racial/ethnic groups, highlighting broad CGM appeal, utilization, and effectiveness across an underprivileged patient population.
Atezolizumab plus anthracycline-based chemotherapy in metastatic triple-negative breast cancer: the randomized, double-blind phase 2b ALICE trial
Authors: Andreas Hagen Røssevold, Nikolai Kragøe Andresen, Christina Annette Bjerre, Bjørnar Gilje, Erik Hugger Jakobsen, Sunil Xavier Raj, Ragnhild Sørum Falk, Hege Giercksky Russnes, Thea Jahr, Randi Ruud Mathiesen, Jon Lømo, Øystein Garred, Sudhir Kumar Chauhan, Ragnhild Reehorst Lereim, Claire Dunn, Bjørn Naume, Jon Amund Kyte
Journal: Nature Medicine (2022)

Abstract Immune checkpoint inhibitors have shown efficacy against metastatic triple-negative breast cancer (mTNBC) but only for PD-L1 positive disease. The randomized, placebo-controlled ALICE trial ( NCT03164993 ) evaluated the addition of atezolizumab (anti-PD-L1) to immune-stimulating chemotherapy in mTNBC. Patients received pegylated liposomal doxorubicin (PLD) and low-dose cyclophosphamide in combination with atezolizumab (atezo-chemo; n = 40) or placebo (placebo-chemo; n = 28). Primary endpoints were descriptive assessment of progression-free survival in the per-protocol population (&gt;3 atezolizumab and &gt;2 PLD doses; n = 59) and safety in the full analysis set (FAS; all patients starting therapy; n = 68). Adverse events leading to drug discontinuation occurred in 18% of patients in the atezo-chemo arm (7/40) and in 7% of patients in the placebo-chemo arm (2/28). Improvement in progression-free survival was indicated in the atezo-chemo arm in the per-protocol population (median 4.3 months versus 3.5 months; hazard ratio (HR) = 0.57; 95% confidence interval (CI) 0.33–0.99; log-rank P = 0.047) and in the FAS (HR = 0.56; 95% CI 0.33–0.95; P = 0.033). A numerical advantage was observed for both the PD-L1 positive ( n = 27; HR = 0.65; 95% CI 0.27–1.54) and PD-L1 negative subgroups ( n = 31; HR = 0.57, 95% CI 0.27–1.21). The progression-free proportion after 15 months was 14.7% (5/34; 95% CI 6.4–30.1%) in the atezo-chemo arm versus 0% in the placebo-chemo arm. The addition of atezolizumab to PLD/cyclophosphamide was tolerable with an indication of clinical benefit, and the findings warrant further investigation of PD1/PD-L1 blockers in combination with immunomodulatory chemotherapy.
Accuracy of Nasal Pressure Swing to Predict Failure of High-Flow Nasal Oxygen in Patients with Acute Hypoxemic Respiratory Failure
Authors: Roberto Tonelli, Andrea Cortegiani, Riccardo Fantini, Luca Tabbì, Ivana Castaniere, Giulia Bruzzi, Stefano Busani, Lorenzo Ball, Enrico Clini, Alessandro Marchioni
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

explored and elucidated the physiological assumptions of the study and defined the study design and procedures.R.T
Transforming terrestrial biodiversity surveys using airborne eDNA
Authors: Kristine Bohmann, Christina Lynggaard
Journal: Trends in Ecology & Evolution (2022)

Studies show that land-living animals, plants, fungi, and bacteria leave DNA traces in the air. These results imply that sequencing of bioaerosols might be a powerful tool for simultaneous surveys of terrestrial biodiversity across lifeforms, but in parallel, it highlights the need to carefully control for possible contaminants.
A phase I/II study of ARO-HSD, an RNA interference therapeutic, for the treatment of non-alcoholic steatohepatitis
Authors: Lung-Yi Mak, Ed Gane, Christian Schwabe, Ki Tae Yoon, Jeong Heo, Russell Scott, Jeong-Hoon Lee, Jung Il Lee, Young Oh Kweon, Martin Weltman, Stephen A. Harrison, Brent A. Neuschwander-Tetri, Kenneth Cusi, Rohit Loomba, Bruce D. Given, Dawn R. Christianson, Eric Garcia-Medel, Min Yi, James Hamilton, Man-Fung Yuen
Journal: Journal of Hepatology (2022)
Evaluation of linear versus star-like polymer anti-cancer nanomedicines in mouse models
Authors: Libor Kostka, Lenka Kotrchová, Eva Randárová, Carolina A. Ferreira, Iva Malátová, Hye Jin Lee, Aeli P. Olson, Jonathan W. Engle, Marek Kovář, Weibo Cai, Milada Šírová, Tomáš Etrych
Journal: Journal of Controlled Release (2022)

Nanomedicines are considered next generation therapeutics with advanced therapeutic properties and reduced side effects. Herein, we introduce tailored linear and star-like water-soluble nanosystems as stimuli-sensitive nanomedicines for the treatment of solid tumors or hematological malignancies. The polymer carrier and drug pharmacokinetics were independently evaluated to elucidate the relationship between the nanosystem structure and its distribution in the body. Positron emission tomography and optical imaging demonstrated enhanced tumor accumulation of the polymer carriers in 4T1-bearing mice with increased tumor-to-blood and tumor-to-muscle ratios. Additionally, there was a significant accumulation of doxorubicin bound to various polymer carriers in EL4 tumors, as well as excellent in vivo therapeutic activity in EL4 lymphoma and moderate efficacy in 4T1 breast carcinoma. The linear nanomedicine showed at least comparable pharmacologic properties to the star-like nanomedicines regarding doxorubicin transport. Therefore, if multiple parameters are considered such as its optimized structure and simple and reproducible synthesis, this polymer carrier system is the most promising for further preclinical and clinical investigations.
Rapid emergence of omicron sublineages expressing spike protein R346T
Authors: Ramona Groenheit, Ilias Galanis, Klara Sondén, Maike Sperk, Elin Movert, Philip Bacchus, Tatiana Efimova, Lina Petersson, Marie Rapp, Viktoria Sahlén, Sandra Söderholm, Karin Valentin Asin, Sarah Zanetti, Maria Lind Karlberg, Andreas Bråve, Jonas Klingström, Kim Blom
Journal: The Lancet Regional Health - Europe (2022)
Risk Factors for Early Onset of Proteinuria in Patients Receiving Atezolizumab Plus Bevacizumab for Unresectable Hepatocellular Carcinoma
Authors: Yuwa Ando, Tomokazu Kawaoka, Masanari Kosaka, Yuki Shirane, Yusuke Johira, Ryoichi Miura, Serami Murakami, Shigeki Yano, Kei Amioka, Kensuke Naruto, Yumi Kosaka, Shinsuke Uchikawa, Kenichiro Kodama, Hatsue Fujino, Takashi Nakahara, Atushi Ono, Eisuke Murakami, Masami Yamauchi, Wataru Okamoto, Shoichi Takahashi, Michio Imamura, Hiroshi Aikata
Journal: Liver Cancer (2022)

Proteinuria is one of the adverse events of atezolizumab plus bevacizumab combination therapy (Atezo + Bev) and can cause interruption in the use of Bev. However, the risk factors for proteinuria in patients with hepatocellular carcinoma (HCC) who are receiving Atezo + Bev have not yet been investigated. The aim of this study was to identify the risk factors for early onset of proteinuria in Atezo + Bev for patients with unresectable HCC.Sixty-four patients with Child-Pugh scores of 5-7, an Eastern Cooperative Oncology Group performance status of 0 or 1, and low level of proteinuria (1+ or less on a dipstick test and urine protein-to-creatinine ratio (UPCR) less than 2.0 g/g Cr) at the initiation of therapy were analyzed. The level of proteinuria was evaluated based on the Common Terminology Criteria for Adverse Events version 5.0. We adopted the UPCR for the quantitative test instead of a 24-h urine collection. The incidence of proteinuria and changes in liver function were retrospectively investigated.The cumulative incidence of proteinuria over a 24-week period was 34.4%. Multivariate analysis showed that a low estimated glomerular filtration rate (hazard ratio [HR], 3.807; 95% confidence interval [CI], 1.579-9.180; p = 0.003), treatment for hypertension (HR, 6.224; 95% CI, 1.614-24.010; p = 0.008), and high systolic blood pressure (SBP) (HR, 2.649; 95% CI, 1.133-6.194; p = 0.025) were risk factors for proteinuria. Serum albumin levels and albumin-bilirubin scores in patients with proteinuria worsened. In addition, a mean SBP ≥135 mm Hg during treatment was the only risk factor for the development of severe proteinuria (UPCR >2 g/g Cr).Our study found that controlling blood pressure is extremely important for the management of proteinuria in patients with HCC who are receiving Atezo + Bev.
Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (monarchE): results from a preplanned interim analysis of a randomised, open-label, phase 3 trial
Authors: Stephen R D Johnston, Masakazu Toi, Joyce O'Shaughnessy, Priya Rastogi, Mario Campone, Patrick Neven, Chiun-Sheng Huang, Jens Huober, Georgina Garnica Jaliffe, Irfan Cicin, Sara M Tolaney, Matthew P Goetz, Hope S Rugo, Elzbieta Senkus, Laura Testa, Lucia Del Mastro, Chikako Shimizu, Ran Wei, Ashwin Shahir, Maria Munoz, Belen San Antonio, Valérie André, Nadia Harbeck, Miguel Martin
Journal: The Lancet Oncology (2022)
Reply to Wennen <i>et al.</i>: Interpretation of Diaphragmatic Force Measurements in Reverse Triggering in a Porcine Model
Authors: L. Felipe Damiani, Laurent J. Brochard
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

"Reply to: Interpretation of Diaphragmatic Force Measurements in Reverse Triggering in a Porcine Model." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp. –
When I use a word . . . . Preventing future deaths—problems and solutions
Authors: Jeffrey K Aronson
Journal: BMJ (2022)

In England and Wales, coroners are legally required to send reports to interested parties when they believe that actions should be taken to prevent deaths other than those on which their conclusions are based. Recipients of the reports are statutorily required to respond to the coroner within 56 days of receiving the report, outlining actions proposed or already taken to tackle the concerns that the coroner has expressed. Similar systems are in operation in Australia and New Zealand. Reports are not, however, uniformly well prepared. Not all recipients respond, and when they do the responses may not be satisfactory. Reports are mainly sent locally and not distributed more widely. Furthermore, recommendations are often not regarded as being sound or practicable or likely to be effective in preventing deaths and injuries. Possible improvements include enhancing the ways in which coroners' reports are produced and made available, ensuring that responses are forthcoming from all those to whom reports are sent, distributing reports more widely, and preparing systematic reviews of collections of similar reports to reinforce the concerns expressed.
Mepitel Film for the Prevention of Acute Radiation Dermatitis in Breast Cancer: A Randomized Multicenter Open-Label Phase III Trial
Authors: Tara Behroozian, Lauren Milton, Irene Karam, Liying Zhang, Keyue Ding, Julia Lou, François Gallant, Eileen Rakovitch, William Tran, Hany Soliman, Eric Leung, Danny Vesprini, Ewa Szumacher, Hanbo Chen, Elysia Donovan, Jacqueline Lam, Silvana Spadafora, Matt Wronski, Chris Lavoie, Natalie Walde, Emily Lam, Gina Wong, Erin McKenzie, Krista Ariello, Samantha Kennedy, Saba Shariati, Katherine Carothers, Glen Gonzales, Yulya Kagan, Edward Chow
Journal: Journal of Clinical Oncology (2022)

Radiation dermatitis (RD) is common in patients undergoing breast radiotherapy. Mepitel film (MF) can reduce RD, but the results from two randomized controlled trials are conflicting. We aimed to conduct a confirmatory randomized controlled trial in patients at risk of RD.Patients were randomly assigned to receive MF or standard care (2:1 ratio). Patients with large breasts after lumpectomy (bra size ≥ 36 inches or cup size ≥ C) or after mastectomy were eligible. Stratification factors included surgery type, dose fractionation, and administration of boost/bolus. The primary end point was grade (G) 2 or 3 RD using the Common Terminology Criteria for Adverse Events v5.0. Secondary end points included patient- and clinician-reported outcomes.Between January 2020 and May 2022, 376 patients were included in the modified intention-to-treat analysis. The incidence of G2 or 3 RD was significantly lower in MF patients compared with standard care (n = 39/251, 15.5%; 95% CI, 11.3 to 20.6% v n = 57/125, 45.6%; 95% CI, 36.7 to 54.8% respectively, odds ratio (OR): 0.20, P < .0001). Benefits of MF remained significant in patients who developed G 3 RD (n = 7, 2.8%; 95% CI, 1.1 to 5.7% v n = 17, 13.6%; 95% CI, 8.1 to 20.9%, OR: 0.19) and moist desquamation (n = 20, 8.0%; 95% CI, 4.9 to 12.0% v n = 24, 19.2%; 95% CI, 12.7 to 27.1%, OR: 0.36). When evaluating the combined patient and health care provider score using Radiation-Induced Skin Reaction Assessment Scale, the MF arm had significantly lower scores (P < .0001). Individual items on the Radiation-Induced Skin Reaction Assessment Scale also favored the MF for both patient- and clinician-reported outcomes. Blistering/peeling, erythema, pigmentation, and edema were significantly reduced in the MF arm. Three patients removed the film prematurely because of rash (n = 2) and excessive pruritus (n = 1).MF significantly reduces RD in patients undergoing breast radiotherapy.
Adjuvant Endocrine Therapy in Premenopausal Breast Cancer: 12-Year Results From SOFT
Authors: Prudence A. Francis, Gini F. Fleming, István Láng, Eva M. Ciruelos, Hervé R. Bonnefoi, Meritxell Bellet, Antonio Bernardo, Miguel A. Climent, Silvana Martino, Begoña Bermejo, Harold J. Burstein, Nancy E. Davidson, Charles E. Geyer, Barbara A. Walley, James N. Ingle, Robert E. Coleman, Bettina Müller, Fanny Le Du, Sibylle Loibl, Eric P. Winer, Barbara Ruepp, Sherene Loi, Marco Colleoni, Alan S. Coates, Richard D. Gelber, Aron Goldhirsch, Meredith M. Regan
Journal: Journal of Clinical Oncology (2022)

JCO
Biofabrication of Modular Spheroids as Tumor‐Scale Microenvironments for Drug Screening
Authors: Naveen Vijayan Mekhileri, Gretel Major, Khoon Lim, Isha Mutreja, Kenny Chitcholtan, Elisabeth Phillips, Gary Hooper, Tim Woodfield
Journal: Advanced Healthcare Materials (2022)

Abstract To streamline the drug discovery pipeline, there is a pressing need for preclinical models which replicate the complexity and scale of native tumors. While there have been advancements in the formation of microscale tumor units, these models are cell‐line dependent, time‐consuming and have not improved clinical trial success rates. In this study, two methods for generating 3D tumor microenvironments are compared, rapidly fabricated hydrogel microspheres and traditional cell‐dense spheroids. These modules are then bioassembled into 3D printed thermoplastic scaffolds, using an automated biofabrication process, to form tumor‐scale models. Modules are formed with SKOV3 and HFF cells as monocultures and cocultures, and the fabrication efficiency, cell architecture, and drug response profiles are characterized, both as single modules and as multimodular constructs. Cell‐encapsulated Gel‐MA microspheres are fabricated with high‐reproducibility and dimensions necessary for automated tumor‐scale bioassembly regardless of cell type, however, only cocultured spheroids form compact modules suitable for bioassembly. Chemosensitivity assays demonstrate the reduced potency of doxorubicin in coculture bioassembled constructs and a ≈five‐fold increase in drug resistance of cocultured cells in 3D modules compared with 2D monolayers. This bioassembly system is efficient and tailorable so that a variety of relevant‐sized tumor constructs could be developed to study tumorigenesis and modernize drug discovery.